Streptococcus Intermedius Brain and Diverticular Abscesses After Dental Manipulation: A Case Report.

A brain abscess is defined as a focal intracerebral infection consisting of an encapsulated collection of pus, which can be a life-threatening complication of infections, trauma, or surgery. While immunocompromised patients can have a wide array of causative organisms, bacterial species represent the most common etiology in immunocompetent individuals. The incidence of brain abscesses ranges from 0.4 to 0.9 per 100,000, with a high predisposition among immunocompromised patients and in those with disruption of the blood-brain barrier. The most common causative organisms found were Streptococcus species, particularly S. viridians and S. pneumonia, Enterococcus, and Staphylococcus species, mainly S. aurieus and S. epidermidis. Microorganism can invade the brain through different mechanisms, either directly by contiguous spread and odontogenic infections, which usually cause a single brain abscess, or indirectly through hematogenous spread which can cause multiple brain abscesses. Both surgical and conservative dental procedures contribute to hematogenous spreading of oral microorganisms. Although most of those organisms are eliminated shortly after they gain access to the bloodstream, some can persist and contribute to the pathogenesis of abscesses in the appropriate environment. Odontogenic origins are rarely implicated in the formation of brain abscesses, and oral foci comprise approximately 5% of identified cases. We report a case of brain and diverticular abscesses due to S. intermidius occurring two months after dental extraction. This case highlights the fact that even usual dental workup can result in the development of bacteremia and disseminated abscesses including but not restricted to the brain. Consequently, in addition to identifying the possible source of bacteremia with an extensive history and physical exam, the diagnosis of Streptococcus milleri organisms should prompt the physicians to screen for sites of possible metastatic infection spread

Modelling of friction stir welding of 304 stainless steel

A 3-D Eulerian steady-state CFD model has been developed to simulate the Friction Stir Welding (FSW) of 6mm plate 304 stainless steel (304SS). The Polycrystalline BoroNitride- Tungsten Rhenium (PCBN-WRe) hybrid tool was modelled with the workpiece in a fully sticking condition. The viscosity of stainless steel was calculated from the flow stress equation taken from a previous study of hot working carried out in a range of temperatures between 800oC-1200 oC and strain rates 0.001 s-1 to 5 s-1. The model predicted the temperature distribution in the Stirred Zone (SZ) for three welding cases including low, intermediate and high rotational speed/traverse speeds. The model also predicts that localised melting may occur if the tool rotational speed exceeds 400RPM. Finally, the model suggested a larger probe (12mm diameter at the shoulder base and 5.8mm length) with a stationary shoulder would prevent the localised melting and allow an increase in welding speeds without the associated introduction of stagnant zone related weld defects

An advanced numerical model of friction stir welding of DH36 steel

A numerical model of Friction Stir Welding (FSW) of DH36 steel plate (6mm thickness) has been developed using a CFD technique. Two welding speed conditions were used, a low welding speed of 200 RPM - 100mm/min, and a high welding speed of 550RPM- 400 mm/min. The heat generation, material flow and strain rate were calculated based on plastic deformation and frictional contact between the tool and workpiece. A CFD-based model has been produced to represent the asymmetry in temperature distribution between the advancing and retreating side, the material flow and the strain rate. The geometry of the model includes the tool plunged into the plate. The cooling system was also included in the simulation by calculating the heat flux lost for each part of the tool. The heat generated by viscous dissipation away from the tool was also taken into account. The total heat generated was divided into the individual tool parts (shoulder, probe side and probe end) and was found to be in good agreement with the experimental results for the areas affected by these parts. The maximum temperature obtained for the slow welding speed was 1012oC and for the high welding speed was 1250oC. Experimental metallographic examination has also been carried out on DH36 FSW steel plates to validate the CFD model. SEM analysis showed the formation of a fine microstructure of bainite, acicular ferrite and ferrite/cementite aggregate in the welded zone as compared to the ferrite/pearlite morphology in the base metal. It is found from the CFD and experimental results that the high speed welding conditions can produce defects such as wormholes and cracks in the welds associated with the probe side and probe end due to the lack of material flow especially on the advancing side. Tensile and fatigue testing were carried out for both slow and high welding speed samples, which broke outside the welded region in the tensile test, however, slow welding speed samples show more resistance to fatigue test and survived 644128 cycles, the high speed welding samples failed after 111,736 cycles under the same load

Wear of polycrystalline boron nitride tool during the friction stir welding of steel

The wear issue of a polycrystalline boron nitride (PCBN) tools during the friction stir welding of two grades of steel, DH36 and EH46, was studied. Two welding traverse and tool rotational speeds were used when welding the DH36 steel. A low tool speed (200RPM, 100 mm/min) and a high tool speed (550RPM, 400 mm/min) were denoted by W1D and W2D, respectively. Nine welding conditions were applied to the welding of EH46 steel plate including seven plunge/dwell trials (W1E–W7E) and two steady-state trials (W8E and W9E). SEM–EDS and XRD tests were applied in order to reveal the boronitride (BN) particles inside the welded joints, and the percentage (%) of BN was calculated according to the standard quantitative metallographic technique. The findings showed that tool wear increases when the tool rotational speed increases as a result of binder softening which is a function of the peak temperature (exceeds 1250 °C) at the tool/workpiece interface. When considering the EH46 steel trials, it was found that an increase in the tool traverse speed in friction stir welding caused a significant tool wear with 4.4% of BN in the top of the stirred zone of W9E compared to 1.1% volume fraction of BN in W8E which was attributed to the higher thermomechanical action on the PCBN tool surface. Tool wear was also found to increase with an increase in tool plunge depth as a result of the higher contact between the surface of friction stir welding tool and the workpiece

p53 inhibitor iASPP is an unexpected suppressor of KRAS and inflammation-driven pancreatic cancer

Oncogenic KRAS activation, inflammation and p53 mutation are key drivers of pancreatic cancer (PC) development. Here we report iASPP, an inhibitor of p53, as a paradoxical suppressor of inflammation and oncogenic KRASG12D-driven PC tumorigenesis. iASPP suppresses PC onset driven by KRASG12D alone or KRASG12D in combination with mutant p53R172H. iASPP deletion limits acinar-to-ductal metaplasia (ADM) in vitro but accelerates inflammation and KRASG12D-induced ADM, pancreatitis and PC tumorigenesis in vivo. KRASG12D/iASPPΔ8/Δ8 tumours are well-differentiated classical PCs and their derivative cell lines form subcutaneous tumours in syngeneic and nude mice. Transcriptomically, either iASPP deletion or p53 mutation in the KRASG12D background altered the expression of an extensively overlapping gene set, comprised primarily of NF-κB and AP1-regulated inflammatory genes. All these identify iASPP as a suppressor of inflammation and a p53-independent oncosuppressor of PC tumorigenesis

Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis

Concurrent mutation of a RAS oncogene and the tumor suppressor p53 is common in tumorigenesis, and inflammation can promote RAS-driven tumorigenesis without the need to mutate p53. Here, we show, using a well-established mutant RAS and an inflammation-driven mouse skin tumor model, that loss of the p53 inhibitor iASPP facilitates tumorigenesis. Specifically, iASPP regulates expression of a subset of p63 and AP1 targets, including genes involved in skin differentiation and inflammation, suggesting that loss of iASPP in keratinocytes supports a tumor-promoting inflammatory microenvironment. Mechanistically, JNK-mediated phosphorylation regulates iASPP function and inhibits iASPP binding with AP1 components, such as JUND, via PXXP/SH3 domain-mediated interaction. Our results uncover a JNK-iASPP-AP1 regulatory axis that is crucial for tissue homeostasis. We show that iASPP is a tumor suppressor and an AP1 coregulator

Defects in Friction Stir Welding of Steel

Defects associated with friction stir welding of two steel grades including DH36 and EH46 were investigated. Different welding parameters including tool rotational and tool traverse (linear) speeds were applied to understand their effect on weld seam defects including microcracks and voids formation. SEM images and infinite focus microscopy were employed to identify the defects types. Two new defects associated with the friction stir welding process are introduced in this work. The first defect identified in this work is a microcrack found between the plunge and the steady state region and attributed to the traverse moving of the tool with unsuitable speed from the plunge-dwell to the steady state stage. The tool traverse speed has recommended to travel 20 mm more with accelerated velocity range of 0.1 from the maximum traverse speed until reaching the steady state. The maximum recommended traverse speed in the steady state was also suggested to be less than 400 mm/min in order to avoid the lack in material flow. The second type of defect observed in this work was microcracks inside the stirred zone caused by elemental precipitations of TiN. The precipitates of TiN were attributed to the high tool rotational speed which caused the peak temperature to exceed 1200 °C at the top of the stirred zone and based on previous work. The limit of tool rotational speed was recommended to be maintained in the range of 200-500 RPM based on the mechanical experiments on the FSW samples

Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment

Hypoxia signaling influences tumor development through both cell-intrinsic and -extrinsic pathways. Inhibiting hypoxia-inducible factor (HIF) function has recently been approved as a cancer treatment strategy. Hence, it is important to understand how regulators of HIF may affect tumor growth under physiological conditions. Here we report that in aging mice factor-inhibiting HIF (FIH), one of the most studied negative regulators of HIF, is a haploinsufficient suppressor of spontaneous B cell lymphomas, particular pulmonary B cell lymphomas. FIH deficiency alters immune composition in aged mice and creates a tumor-supportive immune environment demonstrated in syngeneic mouse tumor models. Mechanistically, FIH-defective myeloid cells acquire tumor-supportive properties in response to signals secreted by cancer cells or produced in the tumor microenvironment with enhanced arginase expression and cytokine-directed migration. Together, these data demonstrate that under physiological conditions, FIH plays a key role in maintaining immune homeostasis and can suppress tumorigenesis through a cell-extrinsic pathway

Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway

Tropheryma whipplei, the etiological agent of Whipple's disease, is an intracellular bacterium that infects macrophages. We previously showed that infection of macrophages results in M2 polarization associated with induction of apoptosis and interleukin (IL)-16 secretion. In patients with Whipple's disease, circulating levels of apoptotic markers and IL-16 are increased and correlate with the activity of the disease. To gain insight into the understanding of the pathophysiology of this rare disease, we examined the molecular pathways involved in T. whipplei-induced apoptosis of human macrophages. Our data showed that apoptosis induction depended on bacterial viability and inhibition of bacterial protein synthesis reduced the apoptotic program elicited by T. whipplei. Induction of apoptosis was also associated with a massive degradation of both pro- and anti-apoptotic mediators. Caspase-specific inhibition experiments revealed that initiator caspases 8 and 10 were required for apoptosis, in contrast to caspases 2 and 9, in spite of cytochrome-c release from mitochondria. Finally, the effector caspases 3 and 6 were mandatory for apoptosis induction. Collectively, these data suggest that T. whipplei induces apoptosis through the extrinsic pathway and that, beside M2 polarization of macrophages, apoptosis induction contributes to bacterial replication and represents a virulence trait of this intracellular pathogen